This work aims to construct biocompatible, biodegradable core-cross-linked and insulin-loaded nanoparticles which are sensitive to glucose and release insulin via cleavage of the nanoparticles in a high-concentration blood glucose environment. First, a polyphosphoester-based diblock copolymer (PBYP-g-Gluc)-b-PEEP was prepared via ring-opening copolymerization (ROP) and the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) in which PBYP and PEEP represent the polymer segments from 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane, respectively, and Gluc comes from 2-azidoethyl-β-d-glucopyranoside (Gluc-N₃) that grafted with PBYP. The structure and molecular weight of the copolymer were characterized by ¹H NMR, ³¹P NMR, GPC, FT-IR, and UV–vis measurements. The amphiphilic copolymer could self-assemble into core–shell uncore-cross-linked nanoparticles (UCCL NPs) in aqueous solutions and form core-cross-linked nanoparticles (CCL NPs) after adding cross-linking agent adipoylamidophenylboronic acid (AAPBA). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to study the self-assembly behavior of the two kinds of NPs and the effect of different Gluc group contents on the size of NPs further to verify the stability and glucose sensitivity of CCL NPs. The ability of NPs to load fluorescein isothiocyanate-labeled insulin (FITC–insulin) and their glucose-triggered release behavior were detected by a fluorescence spectrophotometer. The results of methyl thiazolyl tetrazolium (MTT) assay and hemolysis activity experiments showed that the CCL NPs had good biocompatibility. An in vivo hypoglycemic study has shown that FITC–insulin-loaded CCL NPs could reduce blood glucose and have a protective effect on hypoglycemia. This research provides a new method for constructing biodegradable and glucose-sensitive core-cross-linked nanomedicine carriers for controlled insulin release.

中文翻译：

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用聚磷酸酯二嵌段共聚物构建的葡萄糖敏感核交联纳米颗粒控制胰岛素输送

这项工作旨在构建生物相容性、可生物降解的核心交联和负载胰岛素的纳米颗粒，该纳米颗粒对葡萄糖敏感，并通过在高浓度血糖环境中裂解纳米颗粒来释放胰岛素。首先，通过开环共聚（ROP）和铜（I）催化的叠氮化物-炔环加成（CuAAC）制备聚磷酯基二嵌段共聚物（PBYP- g- Gluc）-b -PEEP，其中PBYP和PEEP代表分别来自 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane 和 2-ethoxy-2-oxo-1,3,2-dioxaphospholane 和 Gluc 的聚合物链段来自 2-叠氮基乙基-β- d-吡喃葡萄糖苷 (Gluc-N ₃) 与 PBYP 嫁接。共聚物的结构和分子量经¹ H NMR、³¹P NMR、GPC、FT-IR 和 UV-vis 测量。两亲性共聚物可以在水溶液中自组装成核壳非核交联纳米粒子（UCCL NPs），并在加入交联剂己基氨基苯基硼酸（AAPBA）后形成核交联纳米粒子（CCL NPs）。采用动态光散射（DLS）和透射电子显微镜（TEM）研究了两种纳米颗粒的自组装行为以及不同Glu基团含量对纳米颗粒尺寸的影响，进一步验证了纳米颗粒的稳定性和葡萄糖敏感性。 CCL NP。通过荧光分光光度计检测纳米颗粒负载异硫氰酸荧光素标记的胰岛素（FITC-胰岛素）的能力及其葡萄糖触发的释放行为。甲基噻唑基四唑（MTT）测定和溶血活性实验结果表明，CCL NPs具有良好的生物相容性。一项体内低血糖研究表明，FITC-胰岛素负载的 CCL NPs 可以降低血糖并对低血糖具有保护作用。该研究为构建可生物降解和葡萄糖敏感的核心交联纳米药物载体以控制胰岛素释放提供了一种新方法。